HIV-1 is the causative agent of AIDS. CD4 is the cellular receptor for HIV-1 and its amino acid sequence is known. The region of HIV-1 that binds to CD-4 is termed gp160 and this is the envelope glycoprotein that is composed of gp120 and gp41. The gp120 region specifically binds to CD4 and the sequences of amino acids in both CD4 and gp120 that are responsible for the high affinity binding of the virus are now known. The interaction of HIV-1 with CD4-bearing cells extends beyond the binding process and there are other events necessary for infection. We have found that the principle neutralizing epitope of HIV-1's gp120 binds sulfated polysaccharides and quite possibly, a highly anionic region of CD4. This region of gp120 is necessary for the infection process and those agents that have been found to block the HIV-1 infection process are probably doing so by a common mechanism. This mechanism involves binding to the highly cationic region of gp120 which extends from amino acids 310 to approximately 330. The significance lies in the fact that complete understanding the molecular processes by which HIV-1 and its target cells interact should lead to a treatment for AIDS that is based on rational drug and vaccine design. New methods in peptide chemistry have been developed as part of this project for the purpose of approaching problems encountered with current synthetic therapeutic and vaccine design strategies.